Promin
Encyclopedia
Promin, or sodium glucosulfone is a sulfone
drug that was investigated for the treatment of malaria
, tuberculosis
and leprosy
. It is broken down in the body to dapsone
, which is the therapeutic form.
in 1940. However, although Parke-Davis did in fact synthesise the compound, it seems certain that they were not the first; in cooperation with J. Wittmann, Emil Fromm synthesised various sulfone compounds in 1908, including both dapsone and some of its derivatives, such as promin. Fromm and Wittmann however were engaged on chemical rather than medical work, and no-one investigated the medical value of such compounds till some decades afterwards. The medical evaluation of sulfones was inspired by the discovery of the unprecedented value of synthetic compounds such as sulfonamides in treating microbial diseases. Early investigations yielded disappointing results, but subsequently promin and dapsone proved valuable in treating mycobacterial diseases. They were the first treatments to show more than a glimmer of hope of controlling such infections.
Initially, Promin appeared to be safer than dapsone, so it was further investigated at the Mayo Clinic
as a treatment for tuberculosis in a guinea pig
model. Because it was already known that leprosy and tuberculosis were both caused by mycobacteria (Mycobacterium leprae
and Mycobacterium tuberculosis
, respectively), Guy Henry Faget
of the National Leprosarium
in Carville, Louisiana, requested information about the drug from Parke-Davis. They, in turn, informed him of the work being done on leprosy in rats by Edmund Cowdry at the Washington University School of Medicine
. His successful results, published in 1941, convinced Faget to begin human studies, both with promin and sulfoxone
sodium, a related compound from Abbott Laboratories
. The initial trials were on six volunteers, and were then expanded and replicated in different locations. Despite severe side effects that caused the initial tests to be suspended temporarily, the drug was shown to be effective. This breakthrough was reported worldwide, and led to a reduction in the stigma attached to leprosy, and consequent better treatment of patients, at the time still referred to as "inmates", and forbidden from using public transport.
Beyond its solubility, however, promin was later found to have no real advantages over the simpler compound dapsone (which is administered in tablet form). Promin and other sulfones can also not be used as substitutes for dapsone when intolerance develops, as this is a general reaction to sulfones, and not specific to dapsone.
Today, the drugs of choice for treating leprosy are dapsone, rifampicin
and clofazimine
.
Sulfone
A sulfone is a chemical compound containing a sulfonyl functional group attached to two carbon atoms. The central hexavalent sulfur atom is double bonded to each of two oxygen atoms and has a single bond to each of two carbon atoms, usually in two separate hydrocarbon substituents.-IUPAC name and...
drug that was investigated for the treatment of malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
, tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
and leprosy
Leprosy
Leprosy or Hansen's disease is a chronic disease caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis. Named after physician Gerhard Armauer Hansen, leprosy is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract; skin lesions...
. It is broken down in the body to dapsone
Dapsone
Dapsone is a medication most commonly used in combination with rifampicin and clofazimine as multidrug therapy for the treatment of Mycobacterium leprae infections . It is also second-line treatment for prophylaxis against Pneumocystis pneumonia caused by Pneumocystis jiroveci Dapsone...
, which is the therapeutic form.
History
The first synthesis of Promin is generally credited to W. H. Feldman of Parke-DavisParke-Davis
Parke-Davis is a subsidiary of the pharmaceutical company Pfizer. Although no longer an independent corporation, it was once America's oldest and largest drug maker, and played an important role in medical history.- History :...
in 1940. However, although Parke-Davis did in fact synthesise the compound, it seems certain that they were not the first; in cooperation with J. Wittmann, Emil Fromm synthesised various sulfone compounds in 1908, including both dapsone and some of its derivatives, such as promin. Fromm and Wittmann however were engaged on chemical rather than medical work, and no-one investigated the medical value of such compounds till some decades afterwards. The medical evaluation of sulfones was inspired by the discovery of the unprecedented value of synthetic compounds such as sulfonamides in treating microbial diseases. Early investigations yielded disappointing results, but subsequently promin and dapsone proved valuable in treating mycobacterial diseases. They were the first treatments to show more than a glimmer of hope of controlling such infections.
Initially, Promin appeared to be safer than dapsone, so it was further investigated at the Mayo Clinic
Mayo Clinic
Mayo Clinic is a not-for-profit medical practice and medical research group specializing in treating difficult patients . Patients are referred to Mayo Clinic from across the U.S. and the world, and it is known for innovative and effective treatments. Mayo Clinic is known for being at the top of...
as a treatment for tuberculosis in a guinea pig
Guinea pig
The guinea pig , also called the cavy, is a species of rodent belonging to the family Caviidae and the genus Cavia. Despite their common name, these animals are not in the pig family, nor are they from Guinea...
model. Because it was already known that leprosy and tuberculosis were both caused by mycobacteria (Mycobacterium leprae
Mycobacterium leprae
Mycobacterium leprae, also known as Hansen’s coccus spirilly, mostly found in warm tropical countries, is a bacterium that causes leprosy . It is an intracellular, pleomorphic, acid-fast bacterium. M. leprae is an aerobic bacillus surrounded by the characteristic waxy coating unique to mycobacteria...
and Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...
, respectively), Guy Henry Faget
Guy Henry Faget
Guy Henry Faget was an American doctor who revolutionalized the treatment of leprosy by demonstrating the efficacy of promin, in a paper reported in 1943. Promin is a sulfone compound synthesized by Feldman and his co-workers in 1940 as an agent against tuberculosis effective in experimental animals...
of the National Leprosarium
National Hansen's Disease Museum
The National Hansen's Disease Museum is a historical museum in Carville, Louisiana at the site of a former sugar plantation and was once home of the Carville National Leprosarium.-History:...
in Carville, Louisiana, requested information about the drug from Parke-Davis. They, in turn, informed him of the work being done on leprosy in rats by Edmund Cowdry at the Washington University School of Medicine
Washington University School of Medicine
Washington University School of Medicine , located in St. Louis, Missouri, is one of the graduate schools of Washington University in St. Louis. One of the top medical schools in the United States, it is currently ranked 4th for research according to U.S. News and World Report and has been listed...
. His successful results, published in 1941, convinced Faget to begin human studies, both with promin and sulfoxone
Sulfoxone
Sulfoxone is an anti-leprosy drug....
sodium, a related compound from Abbott Laboratories
Abbott Laboratories
Abbott Laboratories is an American-based global, diversified pharmaceuticals and health care products company. It has 90,000 employees and operates in over 130 countries. The company headquarters are in Abbott Park, North Chicago, Illinois. The company was founded by Chicago physician, Dr....
. The initial trials were on six volunteers, and were then expanded and replicated in different locations. Despite severe side effects that caused the initial tests to be suspended temporarily, the drug was shown to be effective. This breakthrough was reported worldwide, and led to a reduction in the stigma attached to leprosy, and consequent better treatment of patients, at the time still referred to as "inmates", and forbidden from using public transport.
Pharmacology
Promin is heat-stable and water soluble, and can therefore be heat-sterilized. It can be injected intravenously, and is available in ampules.Beyond its solubility, however, promin was later found to have no real advantages over the simpler compound dapsone (which is administered in tablet form). Promin and other sulfones can also not be used as substitutes for dapsone when intolerance develops, as this is a general reaction to sulfones, and not specific to dapsone.
Today, the drugs of choice for treating leprosy are dapsone, rifampicin
Rifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...
and clofazimine
Clofazimine
Clofazimine is a fat-soluble riminophenazine dye used in combination with rifampicin and dapsone as multidrug therapy for the treatment of leprosy. It has been used investigationally in combination with other antimycobacterial drugs to treat Mycobacterium avium infections in AIDS patients and...
.